..More generally, fuzzy logic models are flexible, able to incorporate qualitative and noisy data, and powerful enough to produce quantitative predictions and new biological insights about the operation of signaling networks...

..Context-specific medium/high throughput proteomic data measured upon perturbation is now relatively easy to obtain but formalisms that can take advantage of these features to build models of signaling are still comparatively scarce...

..We sought to determine whether these databases contain overlapping information and whether they can be used to construct high reliability prior knowledge networks for subsequent modeling of experimental data...

..Taken together, our results show that enhanced MSC osteogenic differentiation corresponds to a sustained combination of receptor expression and ligand presentation, both of which are maintained by tEGF...

A compendium of signals and responses triggered by prodeath and prosurvival cytokines

..We conclude that it is possible to build self-consistent compendia of cell-signaling data that can be mined computationally to yield important insights into the control of mammalian cell responses...

..Activating mutations in K-RAS are common in cancers of the lung, pancreas, and colon and are associated with poor response to therapy. As such, targeted therapies that abrogate K-RAS-induced oncogenicity would be of tremendous value...

..In conclusion, our framework provides a novel approach to understand the multivariate dependencies among molecules in complex networks, and can potentially be used to identify combinatorial targets for therapeutic interventions...

..In sum, using a quantitative approach to study Akt activation identified ligand-dependent limits for the use of T308 or S473 as proxies for kinase activity and suggests the coregulation of Akt phosphorylation and dephosphorylation...

A systems model of signaling identifies a molecular basis set for cytokine-induced apoptosis

..Strut junction interactions affect local directional persistence as well as cell speed at and away from the junctions, providing a new biophysical mechanism for the governance of cell motility by the extracellular microstructure...

..Additional analysis and modeling of the data generated in this study are likely to yield more sophisticated models of receptor tyrosine kinase-initiated signal transduction, trafficking, and regulation...

..Src (pSrc)) at the monolayer, suggesting that the transduction pathway in charge of sensing the mechanical stimulus induced by flow is promoting predetermined mechanically sensitive areas (pSrc) to undergo capillary morphogenesis..

..We anticipate that this model should ultimately be useful in parsing the relative contributions of direct effects of HER2 via signaling vis-a-vis indirect effects of HER2 via modification of EGFR signaling...

..Interpretation of these processes will require mathematical models that are refined in combination with relevant data derived from quantitative assays, to correctly set biophysical objectives for protein design...

..These results support previous studies showing that biophysical cues such as ligand spatial arrangement and extracellular matrix rigidity are central to the governance of cell responses to the external environment...

Migration of tumor cells in 3D matrices is governed by matrix stiffness along with cell-matrix adhesion and proteolysis

..Our experimental findings here represent, to our knowledge, discovery of a previously undescribed set of balances of cell and matrix properties that govern the ability of tumor cells to migration in 3D environments...

A hybrid continuum-discrete modelling approach to predict and control angiogenesis: analysis of combinatorial growth factor and matrix effects on vessel-sprouting morphology

..Our results suggest that the transactivation circuit acts as a context-dependent integrator and amplifier of multiple extracellular signals and that signal integration can effectively occur at multiple points in the EGFR pathway...

..Our experimental data confirm this prediction, demonstrating that cells can use ligand/receptor binding affinity to regulate ligand spatial distribution when autocrine ligand production is limiting for receptor signaling...

..Exogenous TGF-alpha can either enhance or diminish apoptosis in adenoviral vector-treated and TNF-treated hepatocytes, in a biphasic relationship also mediated by autocrine IL-1alpha/beta feedback...

..In agreement with established literature, we show that fibroblasts cultured in the combined device reduced their adhesion strength to the substrate in response to epidermal growth factor stimulation...

..This Fc recycling parameter was found to be correlated with binding affinity, but captures the pH dependent nature of the interaction between Fc and FcRn and may serve as an additional screen following combinatorial experiments...

..The effect of the shRNA-mediated knockdowns in reducing IL-2 production was observed to be stronger than that arising from pharmacological MEK inhibition at comparable degrees of ERK1/2 phosphorylation levels...

..Analysis of IL-7 receptor signaling at a network level in a systematic manner will allow for a comprehensive approach to understanding the impact of multiple signaling pathways on lymphocyte biology...

..Our data suggest that the membrane-anchoring domain of ligands selectively controls their ability to participate in juxtacrine signaling and thus, only a subclass of EGFR ligands can act in a juxtacrine mode...

..Our results show a bimodal dependence of speed and persistence on matrix pore size and suggest high sensitivity on MMP activity, which is in very good agreement with experimental studies carried out in 3D matrices...